Recent studies have demonstrated that the lung is an actively metabolic organ. Significant differences have been shown in the pattern of lung metabolism as compared with other organs. This program is designed to expand the basic knowledge of lung parenchymal metabolism by study of isolated perfused lung, isolated subcellular organelles, and isolated lung cells. The major emphasis will be on glycolytic and oxidative pathways, energy transformation and utilization, and substrate delivery to tissue. Special attention will be given to elucidating differences in metabolic parameters among the various cells comprising the pulmonary parenchyma. During the previous period of support, we investigated the interaction of Ca ions with lung mitochondria, glycolytic flux in the isolated, perfused lung, triose phosphate incorporation into lipids by lung microsomes, redox and energy status of the lung tissue, and the active accumulation and metabolism of serotonin. We will continue investigation of these facets of lung metabolism using the isolated lung and other preparations previously developed. In addition, isolated type II alveolar cells will be studied and compared with results from whole tissue. Substrate utilization and energy status of the pulmonary endothelium will be evaluated using serotonin uptake as a probe. New programs will be initiated to: 1) investigate mixed-function oxidation pathways in lung and its relationship to intermediary metabolism; and 2) to investigate liquid ventilation with dispersed fluorochemical solutions as a means to deliver substrate to alveolar septa. The result will further define the important pathways of substrate utilization and energy generation by the lung and will provide a framework for evaluation of metabolic insults to lung tissue. Provision of substrate via alveolar ventilation may constitute a therapeutic modality for acutely damaged lungs.